Skip to main content
Top
Published in: Journal of Ovarian Research 1/2018

Open Access 01-12-2018 | Research

DAXX promotes ovarian cancer ascites cell proliferation and migration by activating the ERK signaling pathway

Authors: Sheng-Bing Liu, Xue-Ping Lin, Ying Xu, Zhong-Fei Shen, Wei-Wei Pan

Published in: Journal of Ovarian Research | Issue 1/2018

Login to get access

Abstract

Background

The death-domain-associated protein (DAXX) was originally identified as a protein that binds to the transmembrane death receptor FAS and enhances both FAS-induced and transforming growth factor-β-dependent apoptosis. In a previous study, we found that nude mice injected with DAXX-overexpressing cells (ES-2-DAXX) accumulated large concentrations of first-generation ascites cells (I ascites cells). The role of DAXX in the development of ascites is unknown. The aim of this study was to analyze the effect of DAXX on proliferation and migration of ascites cells in ovarian cancer in vitro and in vivo.

Methods

Nude mice were housed in cages with a 14:10 h light:dark cycle; water and food were provided ad libitum. ES-2-DAXX cells (1×106) were injected intraperitoneally into athymic nude mice (8-week-old female mice). After 4 weeks, I ascites cells were collected. The I ascites cells were injected intraperitoneally into athymic nude mice (8-week-old female mice). After 4 weeks, II ascites cells were collected and cultured. Ascites cell survival, migration, and colony formation were measured using colony formation and cell growth assays. Immunofluorescent staining revealed the co-localization of DAXX and promyelocytic leukemia protein (PML) in ascites cell nuclei. Western blotting and immunohistochemistry showed that extracellular signal-related kinase (p-ERK) 1/2 and CEBP-β were highly expressed in tumor tissues formed by II ascites cells. Through immunoprecipitation, we also found that DAXX can interact with CEBP-β.

Results

DAXX enhanced ascites cell survival, migration, and colony formation. DAXX and PML nuclear foci dramatically increased in a passage-dependent manner in ascites cells, DAXX promoted the tumor growth of ascites cells in vivo, increased ascites cell proliferation in vivo, and enhanced ascites cell survival and migration by activating the ERK signalling pathway and integrating with CEBP-β.

Conclusions

DAXX can interact with CEBP-β. DAXX can induce ovarian cancer ascites formation by activating the ERK signal pathway and binding to CEBP-β.
Literature
1.
go back to reference Ozols RF, Bookman MA, Connolly DC, Daly MB, Godwin AK, Schilder RJ, Xu X, Hamilton TC. Focus on epithelial ovarian cancer. Cancer Cell. 2004;5:19–24.CrossRef Ozols RF, Bookman MA, Connolly DC, Daly MB, Godwin AK, Schilder RJ, Xu X, Hamilton TC. Focus on epithelial ovarian cancer. Cancer Cell. 2004;5:19–24.CrossRef
2.
go back to reference Bast RC Jr, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9:415–28.CrossRef Bast RC Jr, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9:415–28.CrossRef
3.
go back to reference Lane D, Robert V, Grondin R, Rancourt C, Piché A. Malignant ascites protect against TRAIL-induced apoptosis by activating the PI3K/Akt pathway in human ovarian carcinoma cells. Int J Cancer. 2007;121:1227–37.CrossRef Lane D, Robert V, Grondin R, Rancourt C, Piché A. Malignant ascites protect against TRAIL-induced apoptosis by activating the PI3K/Akt pathway in human ovarian carcinoma cells. Int J Cancer. 2007;121:1227–37.CrossRef
4.
go back to reference Lane D, Goncharenko-Khaider N, Rancourt C, Piché A. Ovarian cancer ascites protects from TRAIL-induced cell death through αvβ5 integrin-mediated focal adhesion kinase and Akt activation. Oncogene. 2010;29:3519–31.CrossRef Lane D, Goncharenko-Khaider N, Rancourt C, Piché A. Ovarian cancer ascites protects from TRAIL-induced cell death through αvβ5 integrin-mediated focal adhesion kinase and Akt activation. Oncogene. 2010;29:3519–31.CrossRef
5.
go back to reference Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of 6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. Br J Cancer. 2005;92:1475–85.CrossRef Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of 6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. Br J Cancer. 2005;92:1475–85.CrossRef
6.
go back to reference Giuntoli RL, Webb TJ, Zoso A, Rogers O, Diaz-Montes TP, Bristow RE, Oelke M. Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Res. 2009;29:2875–84.PubMed Giuntoli RL, Webb TJ, Zoso A, Rogers O, Diaz-Montes TP, Bristow RE, Oelke M. Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Res. 2009;29:2875–84.PubMed
7.
go back to reference Yigit R, Figdor CG, Zusterzeel PL, Pots JM, Torensma R, Massuger LF. Cytokine analysis as a tool to understand tumour–host interaction in ovarian cancer. Eur J Cancer. 2011;47:1883–9.CrossRef Yigit R, Figdor CG, Zusterzeel PL, Pots JM, Torensma R, Massuger LF. Cytokine analysis as a tool to understand tumour–host interaction in ovarian cancer. Eur J Cancer. 2011;47:1883–9.CrossRef
8.
go back to reference Pan WW, Zhou JJ, Liu XM, Xu Y, Guo LJ, Yu C, Shi QH, Fan HY. Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. J Biol Chem. 2013;288:13620–30.CrossRef Pan WW, Zhou JJ, Liu XM, Xu Y, Guo LJ, Yu C, Shi QH, Fan HY. Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. J Biol Chem. 2013;288:13620–30.CrossRef
9.
go back to reference Dolznig H, Rupp C, Puri C, et al. Modeling Colon Adenocarcinomas in Vitro: A 3D Co-Culture System Induces Cancer-Relevant Pathways upon Tumor Cell and Stromal Fibroblast Interaction. Am J Pathol. 2011;179:487–501.CrossRef Dolznig H, Rupp C, Puri C, et al. Modeling Colon Adenocarcinomas in Vitro: A 3D Co-Culture System Induces Cancer-Relevant Pathways upon Tumor Cell and Stromal Fibroblast Interaction. Am J Pathol. 2011;179:487–501.CrossRef
10.
go back to reference Fischbach C, Kong HJ, Hsiong SX, et al. Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement. Proc Natl Acad Sci U S A. 2009;106:399–404.CrossRef Fischbach C, Kong HJ, Hsiong SX, et al. Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement. Proc Natl Acad Sci U S A. 2009;106:399–404.CrossRef
11.
go back to reference Pickl M, Ries CH. Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab. Oncogene. 2009;28:461–8.CrossRef Pickl M, Ries CH. Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab. Oncogene. 2009;28:461–8.CrossRef
12.
go back to reference Pan WW, Yi FP, Cao LX, Liu XM, Shen Z, Bu Y, Xu Y, Fan HY, Song FZ. DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage. Gene. 2013;526:287–94.CrossRef Pan WW, Yi FP, Cao LX, Liu XM, Shen Z, Bu Y, Xu Y, Fan HY, Song FZ. DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage. Gene. 2013;526:287–94.CrossRef
13.
go back to reference Wethkamp N, Klempnauer KH. Daxx is a transcriptional repressor of CCAAT/enhancer-binding protein β. J Biol Chem. 2009;284:28783–94.CrossRef Wethkamp N, Klempnauer KH. Daxx is a transcriptional repressor of CCAAT/enhancer-binding protein β. J Biol Chem. 2009;284:28783–94.CrossRef
14.
go back to reference Innao P, Pothisuwan M, Pengsa P. Does human epididymis protein 4 (HE4) have a role in prediction of recurrent epithelial ovariancancer. Asian Pac J Cancer Prev. 2016;17:4483–6.PubMed Innao P, Pothisuwan M, Pengsa P. Does human epididymis protein 4 (HE4) have a role in prediction of recurrent epithelial ovariancancer. Asian Pac J Cancer Prev. 2016;17:4483–6.PubMed
15.
go back to reference Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61(3):183–203.CrossRef Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61(3):183–203.CrossRef
16.
go back to reference Auer K, Bachmayr-Heyda A, Sukhbaatar N, Aust S, Schmetterer KG, Meier SM, Gerner C, Grimm C, Horvat R, Pils D. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer. Oncotarget. 2016;7:61336–54.CrossRef Auer K, Bachmayr-Heyda A, Sukhbaatar N, Aust S, Schmetterer KG, Meier SM, Gerner C, Grimm C, Horvat R, Pils D. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer. Oncotarget. 2016;7:61336–54.CrossRef
17.
go back to reference Chen LY, Chen JD. DAXX silencing sensitizes cells to multiple apoptotic pathways. Mol Cell Biol. 2003;23:7108–21.CrossRef Chen LY, Chen JD. DAXX silencing sensitizes cells to multiple apoptotic pathways. Mol Cell Biol. 2003;23:7108–21.CrossRef
18.
go back to reference Yang X, Khosravi-Far R, Chang HY, Baltimore D. DAXX, a novel Fas-binding protein that activates JNK and apoptosis. Cell. 1997;89:1067–76.CrossRef Yang X, Khosravi-Far R, Chang HY, Baltimore D. DAXX, a novel Fas-binding protein that activates JNK and apoptosis. Cell. 1997;89:1067–76.CrossRef
19.
go back to reference Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD. Sequestration and inhibition of DAXX-mediated transcriptional repression by PML. Mol Cell Biol. 2000;20:1784–96.CrossRef Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD. Sequestration and inhibition of DAXX-mediated transcriptional repression by PML. Mol Cell Biol. 2000;20:1784–96.CrossRef
20.
go back to reference Muromoto R, Sugiyama K, Takachi A, Imoto S, Sato N, Yamamoto T, Oritani K, Shimoda K, Matsuda T. Physical and functional interactions between DAXX and DNA methyltransferase 1-associated protein, DMAP1. J Immunol. 2004;172:2985–93.CrossRef Muromoto R, Sugiyama K, Takachi A, Imoto S, Sato N, Yamamoto T, Oritani K, Shimoda K, Matsuda T. Physical and functional interactions between DAXX and DNA methyltransferase 1-associated protein, DMAP1. J Immunol. 2004;172:2985–93.CrossRef
21.
go back to reference Ishov AM, Vladimirova OV, Maul GG. Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternatenuclear sites of the transcription repressor DAXX and SWI/SNF protein ATRX. J Cell Sci. 2004;117:3807–20.CrossRef Ishov AM, Vladimirova OV, Maul GG. Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternatenuclear sites of the transcription repressor DAXX and SWI/SNF protein ATRX. J Cell Sci. 2004;117:3807–20.CrossRef
22.
go back to reference Li R, Pei H, Watson DK, Papas TS. EAP1/DAXX interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. 2000;19:745–53.CrossRef Li R, Pei H, Watson DK, Papas TS. EAP1/DAXX interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. 2000;19:745–53.CrossRef
23.
go back to reference Lehembre F, Müller S, Pandolfi PP, Dejean A. Regulation of Pax3 transcriptional activity by SUMO-1-modifiedPML. Oncogene. 2001;20:1–9.CrossRef Lehembre F, Müller S, Pandolfi PP, Dejean A. Regulation of Pax3 transcriptional activity by SUMO-1-modifiedPML. Oncogene. 2001;20:1–9.CrossRef
24.
go back to reference Lin DY, Lai MZ, Ann DK, Shih HM. Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering DAXX to the PML oncogenic domains (PODs) to enhance its transactivation potential. J Biol Chem. 2003;278:15958–65.CrossRef Lin DY, Lai MZ, Ann DK, Shih HM. Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering DAXX to the PML oncogenic domains (PODs) to enhance its transactivation potential. J Biol Chem. 2003;278:15958–65.CrossRef
25.
go back to reference Zhao LY, Liu J, Sidhu GS, Niu Y, Liu Y, Wang R, Liao D. Negative regulation of p53 functions by DAXX and theinvolvement of MDM2. J Biol Chem. 2004;279:50566–79.CrossRef Zhao LY, Liu J, Sidhu GS, Niu Y, Liu Y, Wang R, Liao D. Negative regulation of p53 functions by DAXX and theinvolvement of MDM2. J Biol Chem. 2004;279:50566–79.CrossRef
26.
go back to reference Salomoni P. The PML-Interacting Protein DAXX: Histone Loading Gets into the Picture. Front Oncol. 2013;3:152.CrossRef Salomoni P. The PML-Interacting Protein DAXX: Histone Loading Gets into the Picture. Front Oncol. 2013;3:152.CrossRef
27.
go back to reference Yu P, Ye L, Wang H, Du G, Zhang J, Zhang J, Tian J. NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways. Tumour Biol. 2015;36:2143–53.CrossRef Yu P, Ye L, Wang H, Du G, Zhang J, Zhang J, Tian J. NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways. Tumour Biol. 2015;36:2143–53.CrossRef
28.
go back to reference Jiang M, Wen F, Cao J, Li P, She J, Chu Z. Genome-wide exploration of the molecularevolution and regulatory network of mitogen-activatedprotein kinase cascades uponmultiple stresses in Brachypodium distachyon. BMC Genomics. 2015;16:228.CrossRef Jiang M, Wen F, Cao J, Li P, She J, Chu Z. Genome-wide exploration of the molecularevolution and regulatory network of mitogen-activatedprotein kinase cascades uponmultiple stresses in Brachypodium distachyon. BMC Genomics. 2015;16:228.CrossRef
29.
go back to reference Knight T, Irving JA. Ras/Raf/MEK/ERK pathway activation in childhood acute lymphoblastic leukemia and its therapeutic targeting. Front Oncol. 2014;4:160.CrossRef Knight T, Irving JA. Ras/Raf/MEK/ERK pathway activation in childhood acute lymphoblastic leukemia and its therapeutic targeting. Front Oncol. 2014;4:160.CrossRef
30.
go back to reference Lee S, Yoon S, Kim DH. A high nuclear basal level of ERK2 phosphorylation contributes to the resistance of cisplatin-resistant human ovarian cancer cells. Gynecol Oncol. 2007;104:338–44.CrossRef Lee S, Yoon S, Kim DH. A high nuclear basal level of ERK2 phosphorylation contributes to the resistance of cisplatin-resistant human ovarian cancer cells. Gynecol Oncol. 2007;104:338–44.CrossRef
31.
go back to reference Goncharenko-Khaider N, Matte I, Lane D, Rancourt C, Piche A. Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2-Elk-1 signaling to attenuate TRAIL-induced apoptosis. Mol Cancer. 2012;11:84.CrossRef Goncharenko-Khaider N, Matte I, Lane D, Rancourt C, Piche A. Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2-Elk-1 signaling to attenuate TRAIL-induced apoptosis. Mol Cancer. 2012;11:84.CrossRef
32.
go back to reference Correa RJ, Peart T, Valdes YR, DiMattia GE, Shepherd TG. Modulation of AKT activity is associated with reversibledormancy in ascites-derived epithelial ovarian cancer spheroids. Carcinogenesis. 2011;33:49–58.CrossRef Correa RJ, Peart T, Valdes YR, DiMattia GE, Shepherd TG. Modulation of AKT activity is associated with reversibledormancy in ascites-derived epithelial ovarian cancer spheroids. Carcinogenesis. 2011;33:49–58.CrossRef
33.
go back to reference Zhu S, Yoon K, Sterneck E, Johnson PF, Smart RC. CCAAT/enhancer binding protein-β is a mediator of keratinocyte survival and skin tumorigenesis involving oncogenic Ras signaling. Proc Natl Acad Sci U S A. 2002;99:207–12.CrossRef Zhu S, Yoon K, Sterneck E, Johnson PF, Smart RC. CCAAT/enhancer binding protein-β is a mediator of keratinocyte survival and skin tumorigenesis involving oncogenic Ras signaling. Proc Natl Acad Sci U S A. 2002;99:207–12.CrossRef
34.
go back to reference Lee HG, Minematsu H, Kim KO, Celil Aydemir AB, Shin MJ, Nizami SA, Chung KJ, Hsu AC, Jacobs CR, Lee FY. Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells. Biomaterials. 2011;32:9197–206.CrossRef Lee HG, Minematsu H, Kim KO, Celil Aydemir AB, Shin MJ, Nizami SA, Chung KJ, Hsu AC, Jacobs CR, Lee FY. Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells. Biomaterials. 2011;32:9197–206.CrossRef
35.
go back to reference Mäuser W, Perwitz N, Meier B, Fasshauer M, Klein J. Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake. Eur J Pharmacol. 2007;564:37–46.CrossRef Mäuser W, Perwitz N, Meier B, Fasshauer M, Klein J. Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake. Eur J Pharmacol. 2007;564:37–46.CrossRef
Metadata
Title
DAXX promotes ovarian cancer ascites cell proliferation and migration by activating the ERK signaling pathway
Authors
Sheng-Bing Liu
Xue-Ping Lin
Ying Xu
Zhong-Fei Shen
Wei-Wei Pan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2018
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-018-0462-4

Other articles of this Issue 1/2018

Journal of Ovarian Research 1/2018 Go to the issue